One form of gene expression impairment by RNA-RNA duplex formation has been termed "antisense" inhibition. This approach to viral therapy is stoichiometric and may require large molar excesses of anti-sense versus target RNA to be effective.
Ribozymes provide antisense molecules which form RNA-RNA hybrids and catalytically cleave the covalent phosphodiester linkages. Ribozymes can be targeted to many RNA transcripts, and efficient cleavage can be achieved in vitro. See, Kim, S. H., et al. Proc. Natl Acad. Sci. U.S.A. 84:8788-8792 (1987); Haseloff, J., et al., Nature 234:585-591 (1988); Cech, T. R. JAMA 260:3030-3034 (1988); Jeffries, A. G., et al., Nucleic Acids Research 17:1371-1377 (1989).
Haseloff, et al. developed a set of rules useful to design transacting ribozymes. The utility of these rules was demonstrated in vitro by ribozymes effectively targeted to different sites within the chloramphenicol acetyltransferase transcript. Haseloff, et al. state that "A major potential application for these highly sequence specific endoribonucleases is in cleavage and thereby inactivation of gene transcripts in vivo. . . . Provided that the transcribed sequences of the gene are known, it should be possible to target one or more ribozymes against specific RNA transcripts. Expression in vivo of such ribozymes and cleavage of the transcripts would in effect inhibit expression of the corresponding gene. This `auto-gene` activity of the ribozymes could provide a basis for various gene and viral therapies and analyses" (pp. 590-591).